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Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis., (© 2024 The Authors.)

Background: Platelet (PLT) product transfusion is a life-saving therapy for actively bleeding patients. There is an urgent need to maintain PLT function and extend shelf life to improve outcomes in these patients. Cold-stored PLT (CS-PLT) maintain hemostatic potential better than room temperature-stored PLT (RT-PLT). However, whether function in long-term CS-PLT is maintained under physiological flow regimes and/or determined by cold-induced metabolic changes is unknown., Objectives: This study aimed to (i) compare the function of RT-PLT and CS-PLT under physiological flow conditions, (ii) determine whether CS-PLT maintain function after 3 weeks of storage, and (iii) identify metabolic pathways associated with the CS-PLT lesion., Methods: We performed phenotypic and functional assessments of RT- and CS-PLT (22 °C and 4 °C storage, respectively; N = 10 unique donors) at storage days 0, 5, and/or 21 via metabolomics, flow cytometry, aggregation, thrombin generation, viscoelastic testing, and a microfluidic assay to measure primary hemostatic function., Results: Day 21 4 °C PLT formed an occlusive thrombus under arterial shear at a similar rate to day 5 22 °C PLT. Day 21 4 °C PLTs had enhanced thrombin generation capacity compared with day 0 PLT and maintained functionality comparable to day RT-PLT across all assays performed. Key metrics from microfluidic assessment, flow cytometry, thrombin generation, and aggregation were associated with 4 °C storage, and metabolites involved in taurine and purine metabolism significantly correlated with these metrics. Taurine supplementation of PLT during storage improved hemostatic function under flow., Conclusion: CS-PLT stored for 3 weeks maintain hemostatic activity, and storage-induced phenotype and function are associated with taurine and purine metabolism., Competing Interests: Declaration of competing interests P.C.S. is a consultant for Cerus Corporation and Haima Therapeutics. All other authors have no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Low-titer group O whole blood (LTOWB) or component therapy (CT) may be used to resuscitate hemorrhaging trauma patients. LTOWB may have clinical and logistical benefits and may improve survival., Objectives: We hypothesized LTOWB would improve 24-hour survival in hemorrhaging patients and would be safe and equally efficacious in non-group O compared with group O patients., Methods: Adult trauma patients with massive transfusion protocol activations were enrolled in this observational study. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour total blood product use. A Cox regression determined the independent associations with 24-hour mortality., Results: In total, 348 patients were included (CT, n = 180; LTOWB, n = 168). Demographics were similar between cohorts. Unadjusted 24-hour mortality was reduced in LTOWB vs CT: 8% vs 19% (P = .003), but 6-hour and 28-day mortality were similar. In an adjusted analysis with multivariable Cox regression, LTOWB was independently associated with reduced 24-hour mortality (hazard ratio, 0.21; 95% CI, 0.07-0.67; P = .004). LTOWB patients received significantly less 72-hour total blood products (80.9 [41.6-139.3] mL/kg vs 48.9 [25.9-106.9] mL/kg; P < .001). In stratified 24-hour survival analyses, LTOWB was associated with improved survival for patients in shock or with coagulopathy. LTOWB use in non-group O patients was not associated with increased mortality, organ injury, or adverse events., Conclusion: In this hypothesis-generating study, LTOWB use was independently associated with improved 24-hour survival, predominantly in patients with shock or coagulopathy. LTOWB also resulted in a 40% reduction in blood product use which equates to a median 2.4 L reduction in transfused products., Competing Interests: Declaration of competing interests P.C.S. is a consultant for Hemanext, Cerus, Haima, and Co-Founder and Chief Medical Officer for Kalocyte. The authors have no other conflicts of interest to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Purpose: Magnetic resonance imaging (MRI) prior to biopsy has improved detection of clinically significant prostate cancer (CaP), but its impact on surgical outcomes is less well established. We compared MRI vs. non-MRI diagnostic pathways among patients receiving radical prostatectomy (RP) for impact on surgical outcomes., Materials and Methods: Men diagnosed with CaP and receiving RP at Loyola University Medical Center (2014-2021) were categorized into MRI or non-MRI diagnostic pathways based on receipt of MRI before prostate biopsy. Primary outcomes of interest included positive surgical margin (PSM) rates, the performance of bilateral nerve-sparing, and biochemical recurrence (BCR). Multivariable logistic regression models, Kaplan-Meier curves, and Cox proportional hazards regression were employed., Results: Of 609 patients, 281 (46.1%) were in the MRI and 328 (53.9%) in the non-MRI groups. MRI patients had similar PSA, biopsy grade group (GG) distribution, RP GG, pT stage, and RP CaP volume compared to non-MRI patients. PSM rates were not statistically different for the MRI vs. non-MRI groups (22.8% vs. 26.8%, P = 0.25). Bilateral nerve-sparing rates were higher for the MRI vs. non-MRI groups (OR 1.95 (95%CI 1.32-2.88), P = 0.001). The MRI group demonstrated improved BCR (HR 0.64 (95%CI 0.41-0.99), P = 0.04) after adjustment for age, PSA, RP GG, pT, pN, and PSM status. On meta-analysis, a 5.2% PSM reduction was observed but high heterogeneity for use of nerve-sparing., Conclusions: An MRI-based diagnostic approach selected patients for RP with a small reduction in PSM rates, greater utilization of bilateral nerve-sparing, and improved cancer control by BCR compared to a non-MRI approach even after adjustment for known prognostic factors., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Subtotal nephrectomy in the rat gives rise to progressive proteinuria, glomerular hypertrophy, and glomerulosclerosis. The proteinuria antedates significant ultrastructural lesions demonstrable by conventional techniques; its mechanism is obscure. In this article it is shown that proteinuria in this system is not accompanied by evident changes in the ultrastructural distribution of anionic sites in the glomerular basement membrane, as determined by organ perfusion with two cationic probe molecules. It is suggested that the proteinuria may reflect a change in the steric aspect of glomerular ultrafilration, in which the loss of renal mass imposes a significant rise in capillary pressure in a structure whose capillaries are peculiar in the high pressures they normally sustain and in their lack of mechanical support from the interstitium. It is suggested that a sustained rise in capillary pressure overcomes the rigidity of the glomerular basement membrane, so that its pore size increases and proteinuria results from basement membrane failure.

The serum of Lewis rats with chronic renal insufficiency (induced by subtotal nephrectomy) contains a nondialyzable inhibitor of the mixed lymphocyte reaction. Fractionation of uremic serum by gel filtration on Sephadex G-200 shows that the inhibitory activity elutes with an apparent molecular weight of greater than 200,000 daltons. To establish the possible relationship of the uremic inhibitor to known immunosuppressive components of normal serum, uremic serum was further fractionated on a DEAE cellulose column. The inhibitory activity elutes in 10 mM sodium phosphate at pH 8.0. This fraction contains both alpha-macroglobulin and IgG. The inhibitory activity of this fraction is completely inactivated by treatment with 2-mercaptoethanol, indicating that the inhibitor is a protein. The inhibitory activity is partially inactivated by periodate treatment, suggesting that it may be a glycoprotein. To determine whether or not the inhibitory factor is an immunoregulatory alpha-macroglobulin, or an immune complex, the uremic serum was fractionated by affinity chromatography procedures, which do not induce artifactual inhibitory properties in control serum. The alpha-macroglobulin was removed by affinity chromatography on a column of Con A-Sepharose; its removal had no effect on the inhibitory activity of serum in the mixed lymphocyte reaction. To examine the possibility that immune complexes may be the uremic inhibitor, the serum was fractionated by affinity chromatography on Protein A-Sepharose or by adsorption to a suspension of Staphylococcus aureus, cowan I. Neither of the two latter procedures had any effect on the inhibitory activity of uremic serum. So far all of our findings indicate that the immunosuppressive factor of uremic serum is distinct from two major immunoregulatory factors, alpha-macroglobulin and immune complexes.

Subtotal nephrectomy in the rat is followed by glomerular hypertrophy, glomerulosclerosis, and, ultimately, renal failure. To gain more insight into this sequence, we have made a morphometric study of the glomerular changes following subtotal nephrectomy in the rat during the period of functional compensation before glomerulosclerosis appears. We found a twofold increase in glomerular volume as compared with controls 2 weeks after operation (to approximately 2 X 10(6) cu mu) followed by a linear increase to approximately 5 X 10(6) cu mu at 21 weeks. The rate of increase in glomerular volume in controls did not significantly exceed that of body weight. The volume increase after subtotal nephrectomy is a true hypertrophy, since other morphometric parameters expressed per unit glomerular volume (surface and length densities) were approximately 80% of control values at 2 weeks and constant thereafter. Glomerular hypertrophy up to 21 weeks is accompanied by a stable BUN and a gradually increasing proteinuria. We conclude that glomerular hypertrophy in this system is a pathologic rather than a compensatory process and suggest that it may represent a counter-productive response to hemodynamic changes serving to increase the glomerular filtration rate.